The objective of these studies is to determine the relationship between the structure and the function of the ribosome in normal and cancerous eucaryotic cells. We will study the role of the ribosome in the following processes: protein synthesis, the control of protein synthesis, RNA synthesis, and the control of RNA synthesis in normal and cancerous eucaryotic cells to determine if there are any differences in these processes between normal and cancerous cells. Nutritional deprivation in conjunction with inhibitors and mutants that affect RNA and protein synthesis will be used to study the control mechanisms of RNA and protein synthesis. These studies will further define the precise mechanisms of RNA and protein metabolism in eucaryotic cells and will lead to a precise understanding of the mechanism of action of the ribosome. The role of the ribosome in RNA and protein synthesis in conditional lethal mutants of eucaryotic cells will be analyzed at the cellular level, in vivo, by the following labeled precursors into DNA, RNA, protein and polysaccharide, polysome stability, and pulse labeled RNA and protein entry into polysomes and other cell components. Differences in RNA and protein metabolism will be studied in vitro by biochemical tests we have developed to characterize conditional lethal mutants defective in protein synthesis in yeast. This approach - first in vivo tests then specific in vitro tests will also enable us to determine the precise mechanism of action of antitumor agents that affect RNA and protein synthesis. Conditional lethal and drug resistant mutants of mammalian cells will be isolated and analyzed to locate their precise defect. BIBLIOGRAPHIC REFERENCES: Peterson, N.S., McLaughlin, C.S. and Nierlich, D.P. Half Life of Yeast Messenger RNA. Nature 260, 70 (1976). Petersen, N.S., McLaughlin, C.S. and Nierlich, D.P. Ribosomal Subunit Entry into Polysomes in Yeast. Biochim. Biophys. Acta. 447, 294-303 (1976).